US-MULT-240253
For moderate to severe rheumatoid arthritis (RA) in adult TNFi-IR patients1
IR=intolerance or inadequate response; TNFi=tumor necrosis factor inhibitor
Limitations of Use: RINVOQ is not recommended for use in combination with other Janus kinase (JAK) inhibitors, biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.1
Awarded the Arthritis Foundation Ease of Use Commendation,2 our innovative bottle cap includes:
IR=intolerance or inadequate response; MTX=methotrexate; RA=rheumatoid arthritis; TNFi=tumor necrosis factor inhibitor
TREATMENT WITH RINVOQ SHOULD NOT BE INITIATED, OR SHOULD BE INTERRUPTED IF:
*Treatment can be initiated or restarted after levels return above specified values, drug-induced liver injury diagnosis is excluded, or infection is controlled.
In RA, PsA, AS, and nr‑axSpA:
No dose adjustment is required for mild, moderate or severe renal impairment.1
No dose adjustment is required for mild or moderate hepatic impairment.1
RINVOQ is not recommended in patients with:
Active hepatitis B or hepatitis C
Severe hepatic impairment (Child‑Pugh C)
RINVOQ has not been studied in end‑stage renal disease (eGFR <15 mL/min/1.73m2)
HYPERSENSITIVITY:1 RINVOQ is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.
Why JAKs are important in RA3-7
Pro-inflammatory cytokines use immune signaling networks, such as the JAK-STAT pathway, to communicate with the cell nucleus. When dysregulated, as in RA, these signals increase the inflammatory response, leading to cycles of chronic inflammation, presenting as pain, swelling, and progressive joint destruction.
Overview of the JAK-STAT pathway3,4,6,8,9
*The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.1
By inactivating JAK, RINVOQ is thought to block the recruitment, phosphorylation, and activation of STATs preventing the pro‑inflammatory cytokine signal from reaching the nucleus and inhibiting pro‑inflammatory processes associated with the JAK‑STAT pathway.
*The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.1
Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK‑1 vs JAK‑2, JAK‑3, and TYK‑2.1,*
EPO=erythropoietin; GH=growth hormone; GM‑CSF=granulocyte‑macrophage colony‑stimulating factor; IFN=interferon; IL=interleukin; JAK=Janus kinase; PsA=psoriatic arthritis; STAT=signal transducer and activator of transcription; TPO=thrombopoietin; TYK=tyrosine kinase
RINVOQ is indicated for the treatment of:
Limitations of Use: RINVOQ is not recommended for use in combination with other Janus kinase (JAK) inhibitors, biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.
Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for ulcerative colitis or Crohn’s disease, or with potent immunosuppressants such as azathioprine and cyclosporine.
REFERENCES
ACR response criteria incorporate physician and patient assessments, as well as acute inflammatory, pain, and physical function measures.
ACR response criteria incorporate physician and patient assessments, as well as acute inflammatory, pain, and physical function measures.
ACR=American College of Rheumatology; CRP=C-reactive protein; HAQ‑Dl=health assessment questionnaire disability index
1. Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum. 1993;36(6):729-740.
2. Uhlig T, Haavardsholm EA, Kvien TK. Comparison of the Health Assessment Questionnaire (HAQ) and the modified HAQ (MHAQ) in patients with rheumatoid arthritis. Rheumatology. 2006;45(4):454‑458.
US-MULT-220500
Adults with moderately to severely active RA and inadequate response or intolerance to bDMARDs.1
RINVOQ is indicated for TNFi-IR patients
aAfter the initial dose, active comparator® IV was administered at 2 and 4 weeks, then every 4 weeks thereafter. The last dose occurred at Week 20. Weight‑based dosing was as follows: <60 kg: 500 mg; 60 - 100 kg: 750 mg; >100 kg: 1000 mg.2
bStarting at Week 12, patients who did not achieve ≥20% improvement in both TJC and SJC compared to baseline at 2 consecutive visits were to have background medication(s) (corticosteroids, NSAIDs, acetaminophen or adding or increasing doses in csDMARD(s)) adjusted or added.1,3
Data not labeled as a ranked secondary endpoint were prespecified nonranked endpoints not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Did not receive any of the protocol-specified bDMARDs prior to entry.
†Based on prednisone equivalent.
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD=biological disease-modifying anti-rheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C-reactive protein; DAS28-CRP=28 joint disease score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; EULAR=European League Against Rheumatism; IV=intravenous; LDA=low disease activity; QD=once per day; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints
1. Rubbert‑Roth A, Enejosa J, Pangan AL, et al. Efficacy and Safety of Upadacitinib vs Abatacept in Patients With Active Rheumatoid Arthritis and Prior Inadequate Response or Intolerance to Biologic Disease‑Modifying Anti‑Rheumatic Drugs (SELECT‑CHOICE): A Double‑Blind, Randomized Controlled Phase 3 Trial. Poster presented at: The European Congress of Rheumatology, 3‑6 June 2020, E‑Congress.
2. Rubbert-Roth A, Enejosa J, Pangan AL, et al. Efficacy and Safety of Upadacitinib vs Abatacept in Patients with Active Rheumatoid Arthritis and Prior Inadequate Response or Intolerance to Biologic Disease‑Modifying Anti‑Rheumatic Drugs (SELECT‑CHOICE): A Double‑Blind, Randomized Controlled Phase 3 Trial. Ann Rheum Dis 2020,79(Supp 1):1011.
3. Data on File. ABVRRTI70957.
4. Data on File. ABVRRTI71850.
US-MULT-220500
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients
aX-ray imaging was performed at these time points; Week 14 for non-responder patients, who were rescued.2,3
bRescue criteria: At Weeks 14, 18 and 22 if <20% improvement in TJC and SJC vs baseline; at Week 26 all remaining PBO patients were switched to RINVOQ, and patients receiving RINVOQ or active comparator were switched to active comparator or RINVOQ, respectively, if CDAI>10.2
cStarting at Week 26, initiation or change in background RA medication(s) including corticosteroids, NSAIDs, or acetaminophen was permitted.4
dStarting at Week 48, patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
eAt Week 48, initiation or change in csDMARDs was allowed, however not all patients received background MTX.5
fPatients continued treatment with UPA or active comparator in a blinded manner until the last patient completed the Week 48 visit and received open-label treatment thereafter.8
At Week 12 vs Placebo + MTX:
At Week 26 vs Placebo + MTX:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs Placebo + MTX. No conclusions regarding this comparison can be made.
*Based on prednisone equivalent
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARDs=biologic disease‑modifying antirheumatic drugs; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C‑reactive protein; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; PBO=Placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once per day; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Fleischmann R, Pangan AL, Song I-H, et al. Supplement - Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double‑blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788‑1800.
3. Fleischmann R, Pangan AL, Song I-H, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double‑blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788‑1800.
4. Data on File. ABVRRTI70534.
5. Data on File. ABVRRTI70955.
6. Data on File. ABVRRTI68439.
7. Upadacitinib meets all primary and ranked secondary endpoints including superiority versus adalimumab in phase 3 study in rheumatoid arthritis. AbbVie Inc. https://news.abbvie.com/news/upadacitinib-meets-all-primary-and-ranked-secondary-endpoints-including-superiority-versus-adalimumab-in-phase-3-study-in-rheumatoid-arthritis.htm. April 9, 2018. August 15, 2019.
8. Fleishmann R, Mysler E, Bessette L, et al. Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis results at 3 years from the SELECT-COMPARE study. Poster presented at: the American College of Rheumatology Convergence, 5-9 November 2021. E-Congress.
9. Data On File. ABVRRTI68440.
10. Data on File. ABVRRTI70956.
11. Fleischmann R, Pangan AL, Mysler E, et al. A phase 3, randomized, double‑blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. Oral presentation at: The ACR annual meeting 2018, 19–24 October 2018, Chicago, USA.
US-MULT-220500
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aPatients on MTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.3
bStarting at Week 26, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDS, acetaminophen or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD including those previously on UPA 30 mg.7
At Week 14:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.
†Prednisone equivalent
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=clinical disease activity index; cMTX=continuous methotrexate; csDMARDs=conventional synthetic disease‑modifying antirheumatic drugs; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C‑reactive protein; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Smolen JS, Pangan AL, Emery P, et al. Supplement - Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2303-2311.
3. Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2303-2311.
4. Smolen JS, Emery P, Rigby W, et al. Upadacitinib as monotherapy in patients with rheumatoid arthritis: results at 48 weeks from the SELECT‑MONOTHERAPY study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
5. Data on File. ABVRRTI68979.
6. Data on File. ABVRRTI68841.
7. A study comparing upadacitinib (ABT-494) monotherapy to methotrexate (MTX) monotherapy in adults with rheumatoid arthritis (RA) who have an inadequate response to MTX (SELECT-MONOTHERAPY). ClinicalTrials.gov identifier: NCT02706951. https://clinicaltrials.gov/ct2/show/NCT02706951. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
Adults with moderately to severely active RA who were MTX‑naïve1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aInitially 947 patients were randomized in the study, but two patients were never dosed.2
bX-ray images of hands and feet obtained at these time points.2
cStarting at Week 12, patients with ≤20% improvement in TJC and SJC compared to baseline at two consecutive visits continued blinded therapy and optimized background RA medications (corticosteroids, NSAIDs, and/or low‑potency analgesics).3,4
dAt Week 26, patients with CDAI≤2.8 continued their original study drug; background medications (NSAIDs, corticosteroids, and/or low‑potency analgesics, and csDMARDs) were optimized in patients with CDAI>2.8 but ≥20% improvement in TJC and SJC; among patients with CDAI >2.8 and <20% improvement in TJC and SJC, RINVOQ 15 mg or upadacitinib 30 mg were added by re‑randomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.2,5
eStarting at Week 48, patients who did not achieve ≥ 20% improvement in both TJC and SJC at two consecutive visits were removed from the study. Initiation of or change in background RA medications (NSAIDs, corticosteroids, low potency analgesics, and csDMARDs; not all patients received background MTX) is allowed at anytime during Period 2.6
fFollowing a protocol amendment, all patients in the long-term extension who were previously receiving UPA 30 mg received UPA 15 mg.11
At Week 12:
At Week 24:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.
ACPA = anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=clinical disease activity index; CR=clinical remission; CRP=C reactive protein; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; JE=joint erosion score; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAIDs=nonsteroidal anti-inflammatory drugs; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. Supplement: Efficacy and safety of upadacitinib monotherapy in methotrexate‑naïve patients with moderately to severely active rheumatoid arthritis (SELECT‑EARLY): a randomized, double-blind, active‑comparator, multi‑center, multi‑country trial. Arthritis Rheumatol. 2020. doi:10.1002/art.41384.
3. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and safety of upadacitinib monotherapy in methotrexate‑naïve patients with moderately to severely active rheumatoid arthritis (SELECT‑EARLY): a randomized, double‑blind, active‑comparator, multi-center, multi‑country trial. Arthritis Rheumatol. 2020. doi:10.1002/art.41384.
4. Data on File. ABVRRTI70661.
5. Data on File. ABVRRTI68563.
6. Data on File. ABVRRTI70953.
7. Van Vollenhoven R, Takeuchi T, Rischmueller M, et al. Upadacitinib monotherapy in methotrexate‑naïve patients with rheumatoid arthritis: results at 72 weeks from SELECT‑EARLY. Poster presented at: The European Congress of Rheumatology, 3‑6 June 2020, E-Congress.
8. Data on File. ABVRRTI68564.
9. Data on File. ABVRRTI70539.
10. Data on File. ABVRRTI70954.
11. A study to compare upadacitinib (ABT-494) monotherapy to methotrexate (MTX) monotherapy in adults with rheumatoid arthritis (RA) who have not previously taken methotrexate (SELECT-EARLY). ClinicalTrials.gov identifier: NCT02706873. https://clinicaltrials.gov/ct2/show/NCT02706873. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDS, acetaminophen or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.4
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.7
At Week 12:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Based on prednisone equivalent
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD= biologic disease‑modifying antirheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying anti-rheumatic drug; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale.
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Burmester GR, Kremer JM, Van den Bosch F, et al. Supplement - Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease‑modifying anti‑rheumatic drugs (SELECT‑NEXT): a randomised, double‑blind, placebo‑controlled phase 3 trial. Lancet. 2018;391(10139):2503‑2512.
3. Burmester GR, Van den Bosch F, Bessette L, et al. Long‑term safety and efficacy of upadacitinib in patients with rheumatoid arthritis and an inadequate response to csDMARDs: results at 60 weeks from the SELECT‑NEXT study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
4. Data on File. ABVRRTI68981.
5. Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease‑modifying anti‑rheumatic drugs (SELECT‑NEXT): a randomised, double‑blind, placebo‑controlled phase 3 trial. Lancet. 2018;391(10139):2503‑2512.
6. Data on File. ABVRRTI68843.
7. Data On File. ABVRRTI73233.
US-MULT-220500
Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, initiation of or change in corticosteroids, NSAIDs, acetaminophen, and csDMARDs was permitted. Patients not achieving response criteria ≥20% improvement in SJC and TJC at two consecutive visits were removed from the study.4,5
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD including those previously on UPA 30 mg.8
At Week 12:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Oral or parenteral methotrexate (7.5-25 mg per week).
†Data available for 168 patients receiving placebo and 161 patients receiving RINVOQ 15 mg.
‡All combinations allowed except MTX and leflunomide.
§Mean MTX dose calculated only for patients receiving MTX.
‖Based on prednisone equivalent.
ACPA=anti‑citrullinated protein antibodies; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARDs=biologic disease‑modifying antirheumatic drugs; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; hsCRP=high‑sensitivity C‑reactive protein; HAQ‑DI=health assessment questionnaire disability index; IL-6=interleukin 6; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36‑item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VAS=visual analog scale
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Genovese MC, Fleischmann R, Combe B, et al. Supplement - Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease‑modifying anti‑rheumatic drugs (SELECT‑BEYOND): a double‑blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513‑2524.
3. Genovese MC, Combe B, Hall S, et al. Upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biologic DMARDs: results at 60 weeks from the SELECT‑BEYOND Study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
4. Data on File. ABVRRTI68669.
5. Data on File. ABVRRTI68670.
6. Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease‑modifying anti‑rheumatic drugs (SELECT‑BEYOND): a double‑blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513‑2524.
7. Data on File. ABVRRTI68842.
8. A study to compare upadacitinib (ABT-494) to placebo in adults with rheumatoid arthritis on stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with an inadequate response or intolerance to biologic DMARDs (SELECT-BEYOND). ClinicalTrials.gov identifier: NCT02706847. https://clinicaltrials.gov/ct2/show/NCT02706847. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
Adults with moderately to severely active RA who had an inadequate response or intolerance to bDMARDs1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, initiation of or change in corticosteroids, NSAIDs, acetaminophen, and csDMARDs was permitted. Patients not achieving response criteria ≥20% improvement in SJC and TJC at two consecutive visits were removed from the study.4,5
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD including those previously on UPA 30 mg.8
At Week 12:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Oral or parenteral methotrexate (7.5-25 mg per week).
†Data available for 168 patients receiving placebo and 161 patients receiving RINVOQ 15 mg.
‡All combinations allowed except MTX and leflunomide.
§Mean MTX dose calculated only for patients receiving MTX.
‖Based on prednisone equivalent.
ACPA=anti‑citrullinated protein antibodies; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARDs=biologic disease‑modifying antirheumatic drugs; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease‑modifying antirheumatic drug; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; hsCRP=high‑sensitivity C‑reactive protein; HAQ‑DI=health assessment questionnaire disability index; IL-6=interleukin 6; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36‑item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; TNFi=tumor necrosis factor inhibitor; VAS=visual analog scale
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Genovese MC, Fleischmann R, Combe B, et al. Supplement - Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease‑modifying anti‑rheumatic drugs (SELECT‑BEYOND): a double‑blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513‑2524.
3. Genovese MC, Combe B, Hall S, et al. Upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biologic DMARDs: results at 60 weeks from the SELECT‑BEYOND Study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
4. Data on File. ABVRRTI68669.
5. Data on File. ABVRRTI68670.
6. Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease‑modifying anti‑rheumatic drugs (SELECT‑BEYOND): a double‑blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513‑2524.
7. Data on File. ABVRRTI68842.
8. A study to compare upadacitinib (ABT-494) to placebo in adults with rheumatoid arthritis on stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) with an inadequate response or intolerance to biologic DMARDs (SELECT-BEYOND). ClinicalTrials.gov identifier: NCT02706847. https://clinicaltrials.gov/ct2/show/NCT02706847. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
Adults with moderately to severely active RA who were MTX‑naïve1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aInitially 947 patients were randomized in the study, but two patients were never dosed.2
bX-ray images of hands and feet obtained at these time points.2
cStarting at Week 12, patients with ≤20% improvement in TJC and SJC compared to baseline at two consecutive visits continued blinded therapy and optimized background RA medications (corticosteroids, NSAIDs, and/or low‑potency analgesics).3,4
dAt Week 26, patients with CDAI≤2.8 continued their original study drug; background medications (NSAIDs, corticosteroids, and/or low‑potency analgesics, and csDMARDs) were optimized in patients with CDAI>2.8 but ≥20% improvement in TJC and SJC; among patients with CDAI >2.8 and <20% improvement in TJC and SJC, RINVOQ 15 mg or upadacitinib 30 mg were added by re‑randomization according to 1:1 ratio for those initially randomized to MTX, and MTX was added for those initially randomized to RINVOQ 15 mg or upadacitinib 30 mg.2,5
eStarting at Week 48, patients who did not achieve ≥ 20% improvement in both TJC and SJC at two consecutive visits were removed from the study. Initiation of or change in background RA medications (NSAIDs, corticosteroids, low potency analgesics, and csDMARDs; not all patients received background MTX) is allowed at anytime during Period 2.6
fFollowing a protocol amendment, all patients in the long-term extension who were previously receiving UPA 30 mg received UPA 15 mg.11
At Week 12:
At Week 24:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Prednisone equivalent dose in patients receiving oral glucocorticoids at baseline.
ACPA = anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=clinical disease activity index; CR=clinical remission; CRP=C reactive protein; csDMARDs=conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; JE=joint erosion score; JSN=joint space narrowing; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; NSAIDs=nonsteroidal anti-inflammatory drugs; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF-36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. Supplement: Efficacy and safety of upadacitinib monotherapy in methotrexate‑naïve patients with moderately to severely active rheumatoid arthritis (SELECT‑EARLY): a randomized, double-blind, active‑comparator, multi‑center, multi‑country trial. Arthritis Rheumatol. 2020. doi:10.1002/art.41384.
3. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. Efficacy and safety of upadacitinib monotherapy in methotrexate‑naïve patients with moderately to severely active rheumatoid arthritis (SELECT‑EARLY): a randomized, double‑blind, active‑comparator, multi-center, multi‑country trial. Arthritis Rheumatol. 2020. doi:10.1002/art.41384.
4. Data on File. ABVRRTI70661.
5. Data on File. ABVRRTI68563.
6. Data on File. ABVRRTI70953.
7. Van Vollenhoven R, Takeuchi T, Rischmueller M, et al. Upadacitinib monotherapy in methotrexate‑naïve patients with rheumatoid arthritis: results at 72 weeks from SELECT‑EARLY. Poster presented at: The European Congress of Rheumatology, 3‑6 June 2020, E-Congress.
8. Data on File. ABVRRTI68564.
9. Data on File. ABVRRTI70539.
10. Data on File. ABVRRTI70954.
11. A study to compare upadacitinib (ABT-494) monotherapy to methotrexate (MTX) monotherapy in adults with rheumatoid arthritis (RA) who have not previously taken methotrexate (SELECT-EARLY). ClinicalTrials.gov identifier: NCT02706873. https://clinicaltrials.gov/ct2/show/NCT02706873. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aPatients on MTX were randomized to receive either RINVOQ 15 mg or upadacitinib 30 mg at Week 14.3
bStarting at Week 26, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDS, acetaminophen or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
cFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD including those previously on UPA 30 mg.7
At Week 14:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Prior to receiving study drug. In the control arm, patients continued prior MTX dose as blinded study drug.
†Prednisone equivalent
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; CDAI=clinical disease activity index; cMTX=continuous methotrexate; csDMARDs=conventional synthetic disease‑modifying antirheumatic drugs; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C‑reactive protein; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Smolen JS, Pangan AL, Emery P, et al. Supplement - Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2303-2311.
3. Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT‑MONOTHERAPY): a randomised, placebo‑controlled, double‑blind phase 3 study. Lancet. 2019;393(10188):2303-2311.
4. Smolen JS, Emery P, Rigby W, et al. Upadacitinib as monotherapy in patients with rheumatoid arthritis: results at 48 weeks from the SELECT‑MONOTHERAPY study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
5. Data on File. ABVRRTI68979.
6. Data on File. ABVRRTI68841.
7. A study comparing upadacitinib (ABT-494) monotherapy to methotrexate (MTX) monotherapy in adults with rheumatoid arthritis (RA) who have an inadequate response to MTX (SELECT-MONOTHERAPY). ClinicalTrials.gov identifier: NCT02706951. https://clinicaltrials.gov/ct2/show/NCT02706951. Updated August 2, 2021. Accessed November 30, 2021.
US-MULT-220500
Adults with moderately to severely active RA who had an inadequate response to csDMARD(s)1
RINVOQ is indicated for TNFi-IR patients
Upadacitinib 30 mg is not an approved dose.
aStarting at Week 24, patients who did not achieve CDAI ≤10 could have initiated or adjusted corticosteroids, NSAIDS, acetaminophen or ≤2 csDMARDs. Patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.4
bFollowing a protocol amendment, all patients in the long-term extension received UPA 15 mg QD, including those previously on UPA 30 mg.7
At Week 12:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
*Based on prednisone equivalent
ACPA=anti‑citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARD= biologic disease‑modifying antirheumatic drug; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; csDMARD=conventional synthetic disease-modifying anti-rheumatic drug; DAS28-CRP=28 joint disease activity score using C-reactive protein; HAQ-DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C-reactive protein; LDA=low disease activity; MTX=methotrexate; NSAIDs=nonsteroidal anti‑inflammatory drugs; PBO=placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once daily; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale.
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Burmester GR, Kremer JM, Van den Bosch F, et al. Supplement - Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease‑modifying anti‑rheumatic drugs (SELECT‑NEXT): a randomised, double‑blind, placebo‑controlled phase 3 trial. Lancet. 2018;391(10139):2503‑2512.
3. Burmester GR, Van den Bosch F, Bessette L, et al. Long‑term safety and efficacy of upadacitinib in patients with rheumatoid arthritis and an inadequate response to csDMARDs: results at 60 weeks from the SELECT‑NEXT study. Poster presented at: The European Congress of Rheumatology, 12‑15 June 2019, Madrid, Spain.
4. Data on File. ABVRRTI68981.
5. Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease‑modifying anti‑rheumatic drugs (SELECT‑NEXT): a randomised, double‑blind, placebo‑controlled phase 3 trial. Lancet. 2018;391(10139):2503‑2512.
6. Data on File. ABVRRTI68843.
7. Data On File. ABVRRTI73233.
US-MULT-220500
Adults with moderately to severely active RA who had an inadequate response to MTX1
RINVOQ is indicated for TNFi-IR patients
aX-ray imaging was performed at these time points; Week 14 for non-responder patients, who were rescued.2,3
bRescue criteria: At Weeks 14, 18 and 22 if <20% improvement in TJC and SJC vs baseline; at Week 26 all remaining PBO patients were switched to RINVOQ, and patients receiving RINVOQ or active comparator were switched to active comparator or RINVOQ, respectively, if CDAI>10.2
cStarting at Week 26, initiation or change in background RA medication(s) including corticosteroids, NSAIDs, or acetaminophen was permitted.4
dStarting at Week 48, patients who failed to show ≥20% improvement in TJC and SJC compared to baseline at 2 consecutive visits were removed from the study.5
eAt Week 48, initiation or change in csDMARDs was allowed, however not all patients received background MTX.5
fPatients continued treatment with UPA or active comparator in a blinded manner until the last patient completed the Week 48 visit and received open-label treatment thereafter.8
At Week 12 vs Placebo + MTX:
At Week 26 vs Placebo + MTX:
Prespecified nonranked endpoints were not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.
SELECT-COMPARE was not designed to evaluate the efficacy of active comparator + MTX vs Placebo + MTX. No conclusions regarding this comparison can be made.
*Based on prednisone equivalent
ACPA=anti-citrullinated protein antibody; ACR=American College of Rheumatology; ACR20=improvement of at least 20% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR50=improvement of at least 50% in tender joint count, swollen joint count, and at least 3 other core criteria; ACR70=improvement of at least 70% in tender joint count, swollen joint count, and at least 3 other core criteria; bDMARDs=biologic disease‑modifying antirheumatic drugs; CDAI=clinical disease activity index; CR=clinical remission; CRP=C‑reactive protein; DAS28-CRP=28 joint disease activity score using C-reactive protein; DAS28-ESR=28 joint disease activity score using erythrocyte sedimentation rate; ESR=erythrocyte sedimentation rate; HAQ‑DI=health assessment questionnaire disability index; hsCRP=high-sensitivity C‑reactive protein; LDA=low disease activity; mTSS=modified total Sharp score; MTX=methotrexate; PBO=Placebo; PhGA=physician’s global assessment of disease activity; PtGA=patient’s global assessment of disease activity; QD=once per day; RA=rheumatoid arthritis; RF=rheumatoid factor; SD=standard deviation; SDAI=simplified disease activity index; SF‑36 (PCS)=36-item short form health survey physical component summary; SJC66=swollen joint count of 66 joints; TJC68=tender joint count of 68 joints; VAS=visual analog scale
1. RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
2. Fleischmann R, Pangan AL, Song I-H, et al. Supplement - Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double‑blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788‑1800.
3. Fleischmann R, Pangan AL, Song I-H, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double‑blind, randomized controlled trial. Arthritis Rheumatol. 2019;71(11):1788‑1800.
4. Data on File. ABVRRTI70534.
5. Data on File. ABVRRTI70955.
6. Data on File. ABVRRTI68439.
7. Upadacitinib meets all primary and ranked secondary endpoints including superiority versus adalimumab in phase 3 study in rheumatoid arthritis. AbbVie Inc. https://news.abbvie.com/news/upadacitinib-meets-all-primary-and-ranked-secondary-endpoints-including-superiority-versus-adalimumab-in-phase-3-study-in-rheumatoid-arthritis.htm. April 9, 2018. August 15, 2019.
8. Fleishmann R, Mysler E, Bessette L, et al. Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis results at 3 years from the SELECT-COMPARE study. Poster presented at: the American College of Rheumatology Convergence, 5-9 November 2021. E-Congress.
9. Data On File. ABVRRTI68440.
10. Data on File. ABVRRTI70956.
11. Fleischmann R, Pangan AL, Mysler E, et al. A phase 3, randomized, double‑blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. Oral presentation at: The ACR annual meeting 2018, 19–24 October 2018, Chicago, USA.
US-MULT-220500
